Lineage Tracing mesoderm progenitors and an in vitro assay to identify niche specific signalling molecules that dictate their cell fate

Abstract

The formation of skeletal muscle during embryonic development requires the fusion of myocytes to form fibres. As muscle grows in the foetus and continues to do so in postnatal life, satellite cells which exist in the peripheries of the fibres continue to divide and supply myogenic cells which can be recruited to the growing muscle and also repair muscle by the same process. A vessel associated population of cells known as pericytes have also been suggested to contribute to peri and postnatal myogenesis. This is a heterogeneous population of cells consisting of an inner layer of perithelial NG2+ cells surrounded by a TNAP+ layer of pericytes which are found in the adventitia. The potency of these pericyte subtypes at varying stages of growth and repair and the factors that influence their fate are still uncertain. Here we show the in vivo lineage tracing of NG2+ and TNAP+ mesoderm progenitors and development of an in vitro assay to test the potency of these cells. We found that TNAP+ progenitors, and to a lesser degree, NG2+ progenitors can contribute to skeletal myogenesis, and contribution of the TNAP+ progenitors increases through postnatal life. Preliminary results from the in vitro assay also show that labelled embryonic mesoderm progenitors are possibly multipotent and can differentiate into both skeletal and smooth muscle as well as endothelium when seeded on feeder layers of these cell types. Our results demonstrate a starting point to the characterisation of the clonal progeny of pericytes and an assessment of their potency through foetal and postnatal development and regeneration. Understanding the myogenic potential of pericytes will help elucidate whether they assist in the regeneration of muscle or contribute to fibrosis and have applications in cell therapies for myopathies such as Duchenne muscular dystrophy.

Date of Award	9 Dec 2021
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Giulio Cossu (Main Supervisor) & Francessco Galli (Co Supervisor)